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重组人肽生长因子、骨形态发生蛋白-7(rhBMP7)和血小板衍生生长因子-BB(rhPDGF-BB)治疗去卵巢大鼠骨质疏松症模型。

Recombinant Human Peptide Growth Factors, Bone Morphogenetic Protein-7 (rhBMP7), and Platelet-Derived Growth Factor-BB (rhPDGF-BB) for Osteoporosis Treatment in an Oophorectomized Rat Model.

机构信息

Cell and Molecular Therapy Group (NUCEL), School of Medicine, University of São Paulo, São Paulo 01246-903, SP, Brazil.

Biotechnology Graduate Program (PPG-USP), University of São Paulo, São Paulo 05508-900, SP, Brazil.

出版信息

Biomolecules. 2024 Mar 7;14(3):317. doi: 10.3390/biom14030317.

Abstract

Bone morphogenetic protein (BMP) and platelet-derived growth factor (PDGF) are known to regulate/stimulate osteogenesis, playing vital roles in bone homeostasis, rendering them strong candidates for osteoporosis treatment. We evaluated the effects of recombinant human BMP-7 (rhBMP7) and PDGF-BB (rhPDGF-BB) in an oophorectomy-induced osteoporosis rat model. Forty Sprague Dawley rats underwent oophorectomy surgery; treatments commenced on the 100th day post-surgery when all animals exhibited signs of osteoporosis. These peptide growth factors were administered intraocularly (iv) once or twice a week and the animals were monitored for a total of five weeks. Two weeks after the conclusion of the treatments, the animals were euthanized and tissues were collected for assessment of alkaline phosphatase, X-ray, micro-CT, and histology. The results indicate that the most promising treatments were 20 µg/kg rhPDGF-BB + 30 µg/kg rhBMP-7 twice a week and 30 µg/kg BMP-7 twice a week, showing significant increases of 15% ( < 0.05) and 13% ( < 0.05) in bone volume fraction and 21% ( < 0.05) and 23% ( < 0.05) in trabecular number, respectively. In conclusion, rhPDGF-BB and rhBMP-7 have demonstrated the ability to increase bone volume and density in this osteoporotic animal model, establishing them as potential candidates for osteoporosis treatment.

摘要

骨形态发生蛋白(BMP)和血小板衍生生长因子(PDGF)已知可调节/刺激成骨作用,在骨稳态中发挥重要作用,使其成为骨质疏松症治疗的有力候选物。我们评估了重组人 BMP-7(rhBMP7)和 PDGF-BB(rhPDGF-BB)在卵巢切除诱导的骨质疏松症大鼠模型中的作用。40 只 Sprague Dawley 大鼠接受卵巢切除术;当所有动物均表现出骨质疏松症迹象时,于手术后第 100 天开始治疗。这些肽生长因子每周经眼内(iv)注射一次或两次,并对动物进行了总共五周的监测。治疗结束两周后,处死动物并收集组织以评估碱性磷酸酶、X 射线、微 CT 和组织学。结果表明,最有前途的治疗方法是每周两次 20µg/kg rhPDGF-BB+30µg/kg rhBMP-7 和每周两次 30µg/kg BMP-7,骨体积分数分别显著增加了 15%(<0.05)和 13%(<0.05),小梁数量分别显著增加了 21%(<0.05)和 23%(<0.05)。总之,rhPDGF-BB 和 rhBMP-7 已证明能够增加这种骨质疏松症动物模型中的骨体积和密度,使其成为骨质疏松症治疗的潜在候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/10968076/89f1ca4ab761/biomolecules-14-00317-g001.jpg

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